Postmortem changes in brain cell structure: a review

Abstract

Brain cell structure is a key determinant of neural function that is frequently altered in neurobiological disorders. Following the global loss of blood flow to the brain that initiates the postmortem interval (PMI), cells rapidly become depleted of energy and begin to decompose. To ensure that our methods for studying the brain using autopsy tissue are robust and reproducible, there is a critical need to delineate the expected changes in brain cell morphometry during the PMI. We searched multiple databases to identify studies measuring the effects of PMI on the morphometry (i.e. external dimensions) of brain cells. We screened 2119 abstracts, 361 full texts, and included 172 studies. Mechanistically, fluid shifts causing cell volume alterations and vacuolization is an early event in the PMI, while loss of cell membrane visualization altogether is a later event. Decomposition rates are highly heterogenous and depend on the methods for visualization, the structural feature of interest, and modifying variables such as the storage temperature or the species. Geometrically, deformations of cell membranes are common early events that initiate within minutes. On the other hand, topological relationships between cellular features appear to be intact for more extended periods. Taken together, there is an uncertain length of time, usually ranging from several hours to several days, over which cell membrane structure is progressively lost. This review may be helpful for investigators studying human postmortem brain tissue, wherein the PMI is an unavoidable aspect of the research.

Volume electron microscopy reveals 3D synaptic nanoarchitecture in postmortem human prefrontal cortex

“…These proportions are highly consistent with findings in layer 3 of biopsied temporal cortex 3 80 , but lower than the findings of 92-95% Type 1 synapses in postmortem temporal cortex layers 2 – 5 81,85–89 and anterior cingulate cortex layer 3 85 . Findings regarding the effects of PMI on Type 1 and 2 synapse identification are highly mixed (for review see 91 ). Some evidence suggests that PSD size may increase with PMI 92 , resulting in the possible mis-identification of Type 2 synapses as Type 1.…”

Effects of autolysis and prolonged formalin fixation on histomorphology and immunohistochemistry of normal canine brain tissue: an experimental study

“…1), consistent with reported criteria. 4,5,10,14,15,19,20,22 The primary observed changes were 1) increased coarseness to fine vacuolation of the neuroparenchyma; 2) nuclear changes, including loss of chromatin detail, loss of distinction of the nuclear membrane, and pyknosis; 3) cytoplasmic shrinkage, loss of neuronal Nissl substance, and artifactual pericellular clear space around glial cells and neurons; and 4) increased overall amphophilic staining of the neuroparenchyma. The most striking and easily recognized of these changes were parenchymal vacuolation, nuclear pyknosis, and pericellular clear space (especially noticeable around oligodendroglia and small neurons of the cerebellar granular layer).…”

Dopaminergic neuronal death via necroptosis in Parkinson's disease: A review of the literature

“…However, studying autopsy tissue can present significant confounds due to premortem and postmortem conditions that may influence tissue quality and its ability to yield accurate results. Recognized confounds that reduce tissue quality are agonal factors (e.g., coma, hypoxia and hyperpyrexia at the time of death) and long postmortem interval (Krassner et al, 2023; Kretzschmar, 2009; Nagy et al, 2015; Samarasekera et al, 2013; Stan et al, 2006). With this caveat in mind, we revise the main findings from studies on programmed cell death mechanisms and necroptosis in human brain tissues.…”